The primary objective of this project is to search for genes associated with peak bone density as a risk factor for osteoporotic fractures. Primary osteoporosis is characterized by increased susceptibility to fractures. A potentially modifiable risk factor for osteoporotic fractures is low bone density. Preliminary studies have indicated that the majority of variation in peak bone density is determined by genetic factors and there are significant genetic factors influencing skeletal architecture which are also related to the risk for osteoporotic fractures. These studies will therefore concentrate upon the search for genetic factors which determine peak bone density and skeletal architecture. Past studies have concentrated on twins to estimate heritability and search for evidence of the modes of inheritance of these osteoporosis risk factors. We have recently begun a study of sibling pairs (sibpairs) to begin a genome wide search for genetic markers linked to bone density, skeletal architecture and intermediate phenotypes related to bone metabolism. Positive findings will map loci which are in close proximity to or within genes which influence these quantitative traits. We plan to extend studies of approximately 200 Caucasian, adult, female sibpairs begun in the 09 and 10 years of the present granting period with the addition of 300 more Caucasian sibpairs and 250 African American sibpairs during years 11 through 15 of the project. The genetic markers being used are the highly informative (dC-dA)n.(dC-dT)n microsatellites.